Abstract
BackgroundCholangiocarcinoma is an aggressive tumor with a tendency for local invasion and distant metastases. Timely diagnosis is very important because surgical resection (R0) remains the only hope for a cure. However, at present, there is no available tumor marker that can differentiate cholangiocarcinoma from benign bile duct disease. Previous studies have demonstrated that matrix metalloproteinase (MMP)-7 and MMP-9 are frequently expressed in cholangiocarcinoma specimens.MethodsThis study was designed to determine whether the serum levels of MMP-7 and MMP-9 can discriminate cholangiocarcinoma patients from benign biliary tract disease patients in comparison to carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9). We measured the level of CEA, CA19-9, MMP-7 and MMP-9 in the serum of 44 cholangiocarcinoma and 36 benign biliary tract diseases patients.ResultsAmong the serum levels of CEA, CA19-9, MMP-7 and MMP-9, only the serum MMP-7 level was significantly higher in the patients with cholangiocarcinoma (8.9 ± 3.43 ng/ml) compared to benign biliary tract disease patients (5.9 ± 3.03 ng/ml) (p < 0.001). An receiver operating characteristic (ROC) curve analysis revealed that the detection of the serum MMP-7 level is reasonably accurate in differentiating cholangiocarcinoma from benign biliary tract disease patients (area under curve = 0.73; 95% CI = 0.614–0.848). While the areas under the curve of the ROC curves for CEA, CA19-9 and MMP-9 were 0.63 (95% CI = 0.501–0.760), 0.63 (95% CI = 0.491–0.761) and 0.59 (95% CI = 0.455–0.722), respectively.ConclusionSerum MMP-7 appears to be a valuable diagnostic marker in the discrimination of cholangiocarcinoma from benign biliary tract disease. Further prospective studies for serum MMP-7 measurement should be carried out to further investigate the potential of this molecule as a biomarker of cholangiocarcinoma.
Highlights
Cholangiocarcinoma is an aggressive tumor with a tendency for local invasion and distant metastases
Thirty-six patients were diagnosed with benign biliary tract diseases, and 44 patients were diagnosed as having cholangiocarcinoma by one of the following criteria: 1) tissue biopsy (n = 7), 2) cytology (n = 17), and 3) radiological finding and clinical observation to identify the progression of the tumor at follow up (n = 20)
We used a carcinoembryonic antigen (CEA) cut-off value of 5 ng/ml and a carbohydrate antigen 19-9 (CA19-9) cut-off value of 100 U/ml because these have been the suggested cut-off value for the diagnosis of cholangiocarcinoma [7]
Summary
Cholangiocarcinoma is an aggressive tumor with a tendency for local invasion and distant metastases. At present, there is no available tumor marker that can differentiate cholangiocarcinoma from benign bile duct disease. The incidence of and mortality rate for cholangiocarcinoma varies considerably among different geographic regions, with the highest incidence being observed in Southeast Asia, especially in Thailand [1]. In the United States, the most commonly recognized risk factor for cholangiocarcinoma is primary sclerosing cholangitis (PSC) [2,3]. In Southeast Asia and especially in Thailand, infection with hepatobiliary flukes (Opisthorchis viverrini) is the most common risk factor for cholangiocarcinoma [4]. Five-year survival, which typically has a rate between 32% and 50%, is achieved by only a small number of patients when negative histological margins are attained at the time of surgery [5]. To improve the survival rate, patients must be diagnosed and treated as early in the disease onset as possible
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